Corticosteroids for vulvar lichen sclerosus.
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Administration, Topical↗
Biomedical subjects
L Edwards
Publications and source records attributed to L Edwards.
Development of the Royal Marsden Hospital paediatric oncology quality of life questionnaire.
Our objective was to develop a health-related quality of life measure for use in pediatric oncology. The development process followed the EORTC Quality of Life Study Group (QLSG) guidelines but utilized a parental proxy rating methodology developed within the framework of the EORTC QLSG. Data are reported on the preliminary stages of development, which include interviews in the target population, specialist review of questionnaire content and initial results on the psychometric structure of the measure. The questionnaire has been translated from English to Swedish and Dutch and is available for international field testing. Suggestions for further development of the new measure are described, including the need for parallel forms for use with children and adolescents as well as the parental proxy rating form described here.
Child↗
Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus.
OBJECTIVE: To compare the safety and effectiveness of 5% and 1% imiquimod cream with vehicle cream in the treatment of external anogenital warts. DESIGN: Randomized, double-blind, placebo-controlled comparison that evaluated patients for total clearance of their warts. Patients who experienced total clearance were evaluated for recurrence in a 12-week follow-up. SETTING: Eleven ambulatory offices, including both private physician offices and referral medical centers. PATIENTS: Three hundred eleven healthy men and women aged 18 years or older with 2 to 50 external anogenital warts were recruited from the practices of investigators, referring physicians, and advertisements. Eighty-two additional patients were screened but did not qualify. Four patients discontinued use of the medication because of adverse effects. INTERVENTIONS: Five percent imiquimod (Aldara) cream, 1% imiquimod cream, or vehicle cream was applied to all external warts overnight 3 times each week for 16 weeks, or until all treated warts disappeared, whichever occurred first. MAIN OUTCOME MEASUREMENTS: The number of patients experiencing the elimination of all baseline warts and the recurrence rate of these warts. In addition, the reduction in baseline wart area the duration of therapy required to eliminate warts, and the frequency and severity of adverse reactions were principal measurements. RESULTS: In the intent-to-treat analysis, 54 (50%) of 109 patients who received 5% imiquimod cream, 21 (21%) of 102 of those who received 1% imiquimod cream, and 11 (11%) of 100 patients treated with vehicle cream experienced eradication of all treated baseline warts. The difference between the effectiveness of 5% imiquimod cream and the vehicle cream was statistically significant (P < .001). Of those patients whose warts cleared during therapy, 13% of patients who received 5% imiquimod experienced a recurrence of at least 1 wart. Recurrences occurred in none of the patients who used 1% imiquimod cream and in 10% of patients who used the vehicle cream. Local erythema was the most common adverse reaction, but the majority of patients in each group experienced no or only mild local inflammatory reactions. There were no differences in incidences of flulike symptoms among treatment groups. CONCLUSIONS: Five percent imiquimod cream is an effective and safe self-administered therapy for external anogenital warts when applied 3 times a week overnight for up to 16 weeks. The recurrence rate is low.
Adjuvants, Immunologic↗
Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts.
OBJECTIVE: To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts. DESIGN: Double-blind, randomized, multicenter, vehicle-controlled investigation. SETTING: Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations. PATIENTS: Three hundred twenty-six patients with anogenital warts. MAIN OUTCOME MEASURE: Number of patients with clearing of all treated warts (treatment success). RESULTS: The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions. CONCLUSIONS: The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.
Administration, Cutaneous↗
Evaluating the potential and problems of three-dimensional computed tomography measurements of arterial stenosis.
Volume visualization is gaining widespread acceptance in medical applications. As its use increases, the issue of accuracy becomes critical. There have been very few studies examining the accuracy of volume rendering techniques. We studied the accuracy of hardware-assisted volume rendering for measurement of arterial stenosis in computed tomography (CT) data. The results of our study reveal that accurate measurements can be made from volume rendered CT data. However, error is present (absolute average error from 5.1% to 13.6%) and there is some variability, even for experts (standard deviation ranged from 4.8% to 15%). The evidence suggests that the choice of volume rendering (transfer function) parameters greatly affects the accuracy of the results. Accurate transfer function parameter selection is a difficult problem. Parameters that produce realistic images often provide inaccurate measurements. As the use of volume visualization grows and more inexperienced users begin using these tools for medical diagnosis and staging, new guidelines, aids, and techniques must be developed to ensure reliable, accurate visualization results.
Angiography↗
Care of the suddenly bereaved in cardiac care units: a review of the literature.
This paper considers the experiences emerging from relatives whose loved ones die suddenly in a Cardiac Care Unit (CCU). It examines how best to address their needs and how to facilitate the normal grieving process during their brief yet traumatic hospital encounter. There appears to be no primary research relating specifically to sudden bereavement in a CCU. Several authors assume that findings can be applied between specialties but there is no empirical evidence to support this assumption. The research which does exist is predominantly in the areas of bereavement generally and in Accident and Emergency (A&E) in particular. This paper contains a critical examination of this literature and consideration of the extent to which findings from these fields can be relied upon to lead practice in the CCUs. It is concluded that recommendations for practice arising from such literature, e.g. those supporting the allocation of an advocate nurse to accompany relatives and allowing observation of resuscitation, may not be readily applicable to CCUs. The paper concludes with a consideration of future cardio-specific research needs.
Bereavement↗
A continuum of neutrophilic disease occurring in a patient with ulcerative colitis.
A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) occurring concurrently with bullous pyoderma gangrenosum is reported to emphasize the close relationship between these two disorders. Atypical pyoderma gangrenosum and Sweet's syndrome have been described as occurring simultaneously in haematological dyscrasias but not, to our knowledge, in ulcerative colitis. It has been proposed that pyoderma gangrenosum, Sweet's syndrome, erythema elevatum diutinum and subcorneal pustular dermatosis may represent manifestations along a continuum of neutrophilic dermatoses.
Biopsy, Needle↗
Extraovarian endometrioid carcinoma associated with unopposed oestrogen replacement therapy.
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Carcinoma, Endometrioid↗
The SF36 as an outcome measure of services for end stage renal failure.
OBJECTIVE: To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. SUBJECTS AND METHODS: 660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two "role" dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care.
Data Collection↗
Computational models for the formation of protocell structures.
There have been various attempts to simulate the self-assembly process of lipid aggregates by computers. However, due to the computationally complex nature of the problem, previous simulations were often conducted with unrealistic simplifications of the molecules' morphology, intermolecular interactions, and the environment in which the lipid molecules interact. In this article, we present a new computational model in which each lipid is simulated by a more realistic amphiphilic particle consisting of a hydrophilic head and a long hydrophobic tail. The intermolecular interactions are approximated by a set of simple forces reflecting physical and chemical properties of lipids, for example, hydrophobicity and electrostatic forces, which are believed to be crucial for the formation of various aggregates. With a set of carefully selected parameters, this model is able to simulate successfully the formation of micelles in an aqueous environment and reversed micelle structures in an oil solvent from an initially randomly distributed set of lipidlike particles. This model can be used to study, at the microscopic level, the self-assembly of different protocell structures in the evolutionary process and the impact of environmental conditions on the formation of these structures. It may be further generalized to simulate the formation of other, more complex structures of amphiphilic molecules such as monolayer and bilayer aggregates.
Catalysis↗
Imiquimod in clinical practice.
Applied topically, imiquimod induces the production of interferon-alpha plus other cytokines. Because intralesional interferon is effective in the treatment of condylomata acuminata (genital warts), topical imiquimod has also been investigated as a potential therapy for this condition. The dosing regimen found to best balance efficacy, side-effects and practicality is 5% imiquimod cream applied overnight by the patient three times weekly until warts clear, for up to 16 weeks. The largest double-blind trial to examine this protocol involved 311 patients with external anogenital warts who were randomized to use imiquimod 5% cream, imiquimod 1% cream or vehicle cream. Evaluation of all patients given medication at any time showed that 50% of those who received 5% imiquimod experienced clearing of all baseline warts, as compared to 21% of those who used 1% imiquimod and 11% of those treated with vehicle. Overall, 5% imiquimod treatment was significantly more effective than vehicle (P < 0.0001). Excluding patients who discontinued medication for reasons unrelated to therapy (such as moving out of town or poor compliance), 56% of those who received 5% imiquimod experienced complete clearing of baseline warts. Clearing also occurred in 27% of those who received imiquimod 1%. Recurrence of baseline warts occurred in 13% of patients whose warts cleared with 5% imiquimod. When applied overnight at home three times each week, topical imiquimod 5% cream is an effective therapy with acceptable side-effects. The recurrence rate is low and further studies to specifically compare recurrence rates are warranted.
Adjuvants, Immunologic↗
Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways.
STUDY OBJECTIVES: Airway epithelial ion transport is an important component of the airway defense mechanism, and new therapies that target ion transport are being developed. Amiloride is an example of such a new drug, exerting a dose-dependent action to inhibit Na+ transport. Amiloride may be useful in cystic fibrosis, blocking the characteristic airway epithelial Na+ hyperabsorption that occurs in the disease. To evaluate airway and systemic delivery of amiloride via an ultrasonic nebulizer (Omron NE-UO7), we measured the airway surface concentrations of amiloride in normal volunteers via a novel approach, together with the systemic pharmacokinetics of amiloride. DESIGN: Direct measurement of airway surface liquid, plasma, and urine amiloride concentrations following ultrasonic nebulization. PARTICIPANTS/INTERVENTIONS: Seven normal subjects were studied in the General Clinical Research Center of the University of North Carolina. Following inhalation with amiloride (1 mg/mL, 4.5 mL) for approximately 12 min, a bronchoscopy was performed. Amiloride deposition and clearance from airway surfaces over 1 h were evaluated by transbronchoscopic sampling using preweighed filter papers. Pulmonary and systemic absorption was assessed by measuring drug concentrations in blood and urine. RESULTS: The mean volume aerosolized was 3.5+/-0.3 mL during 12 min of aerosolization time; the mean initial concentration of amiloride on airway surfaces after nebulization was 1.6 x 10(-4) mol/L, with an elimination half life of approximately 23 min. Peak plasma concentrations of amiloride (30 min, 3.36+/-0.70 ng/mL) suggest early absorption across lung surfaces, rather than via the GI route. Mean urinary excretion of amiloride over 72 h was 0.63+/-0.07 mg, with 87% excreted in the first 24 h. CONCLUSIONS: The ultrasonic nebulizer rapidly delivers amiloride to normal conducting airways as assessed by the transbronchoscopic sampling technique. Early blood concentrations of amiloride probably reflect initial absorption across lung surfaces and are a useful index of the efficiency of the machine.
Absorption↗
Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis.
BACKGROUND: Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but severity of lung disease and rate of lung function decline are widely variable. Accurate estimates of decline have been difficult to define and compare because the timing of measurements and duration of follow-up differ in various patient groups. PATIENTS: Three hundred sixty-six patients with CF, born from 1960 to 1974, were selected from a CF database birth cohort if they had two or more measurements of pulmonary function, at least one of which was performed before the age of 10 years. METHODS: Mixed model regression analysis provided estimates of the average rate of decline of spirometry measurements in subgroups on the basis of survival age, sex, pancreatic status, and genotype. RESULTS: Patients who died before the age of 15 years had significantly poorer pulmonary function when first tested and a more rapid decline in pulmonary function thereafter than patients who survived beyond the age of 15 years. In the latter, functional levels at the age of 5 years were normal, but average rates of decline were significantly related to survival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper decline than those with pancreatic sufficiency. In the subset of 197 who survived to 1990 and were subsequently genotyped, rate of decline was greater in those homozygous for the delta F508 mutation, compared with those who were heterozygous for delta F508 or those, who had two other mutations. DISCUSSION: All but the most severely affected patients, who died before age 15, appear to have had normal pulmonary function when first tested in early childhood. Pancreatic sufficiency, male gender, and some non-delta F508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable tool for describing and comparing pulmonary function decline in groups of patients with CF.
Adolescent↗
Fluticasone propionate powder administered through Diskhaler versus triamcinolone acetonide aerosol administered through metered-dose inhaler in patients with persistent asthma.
BACKGROUND: Attempts to delineate efficacy and safety differences among inhaled corticosteroids have been difficult because of the lack of well-controlled, comparative studies reported in the medical literature. METHODS: A randomized, double-blind, double-dummy study was conducted in 24 outpatient centers. A total of 291 male and female patients at least 12 years of age with asthma (FEV1 between 50% and 80% of predicted value), who had previously received maintenance therapy with beclomethasone dipropionate or triamcinolone acetonide, were switched to treatment with fluticasone propionate powder (250 microg twice daily), triamcinolone acetonide aerosol (200 microg four times daily), or placebo for 24 weeks. RESULTS: Mean increase in FEV1 from baseline to end point was significantly (p = 0.009) greater in patients switched to treatment with fluticasone compared with patients switched to treatment with triamcinolone (0.27 L and 0.07 L, respectively). At end point, mean increase in morning peak expiratory flow from baseline was 21 L/min with fluticasone compared with mean decreases of 6 L/min and 28 L/min with triamcinolone and placebo, respectively (p < 0.001 vs triamcinolone and placebo). Supplemental rescue albuterol use decreased by 30% from baseline with fluticasone (p < 0.05 vs triamcinolone and placebo) compared with triamcinolone (6%) or placebo (increased by 50%). The percentage of patients withdrawn from the study because they met predefined lack-of-efficacy criteria was higher with placebo (60%) and triamcinolone (27%) than with fluticasone (17%). Incidence of adverse events and low morning plasma cortisol concentrations were similar across treatment groups except for oral candidiasis (p = 0.035, fluticasone vs placebo). CONCLUSION: Fluticasone propionate powder twice daily (500 microg/day) was superior in efficacy to triamcinolone acetonide aerosol four times daily (800 microg/day) in patients with persistent asthma.
Administration, Inhalation↗
How do we increase awareness of osteoporosis?
In the UK and throughout Europe 10 years ago, osteoporosis was not a word that existed in the vocabulary of the general public. The majority of doctors had dismissed osteoporosis as a normal process of ageing, affecting only the very elderly and about which nothing could be done. Why should it matter that awareness of osteoporosis was so low among the general public and the medical professions? For the newly launched National Osteoporosis Society in the UK, several questions needed to be answered: if osteoporosis was not an inevitable part of growing old, was it really a disease and how could action be implemented to treat it and prevent it? If fracture numbers and their costs were so much higher than had been thought, who should be informed of this? And if there were ways of treating and preventing osteoporosis, who should be made more aware, what should they be told, and how could such awareness-raising be done and paid for? Before real action could be undertaken, a considerable awareness programme would be needed to radically-alter traditional beliefs about bone health.
Clinical Competence↗
Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.
OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.
Analysis of Variance↗
Eczema/dermatitis: management & tips.
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Adrenal Cortex Hormones↗
Childhood sexual and physical abuse. Incidence in patients with vulvodynia.
OBJECTIVE: To compare the incidence of sexual and/or physical abuse in women with vulvodynia (chronic, burning vulvar pain in the absence of clear medical findings) as compared to women with chronic vulvar symptoms due to specific, objective vulvar disease and with women from a general dermatology practice. STUDY DESIGN: An invitation to participate in this questionnaire study was sent to 300 women over 18 years of age from a vulvo-vaginal clinic and 280 women from a general dermatology practice. These questionnaires asked for basic demographic information as well as information on childhood sexual experiences and physical abuse. RESULTS: Questionnaires from 89 patients with vulvodynia, 65 patients with chronic vulvar symptoms due to specific, objective vulvar disease and 166 patients from a general dermatology practice were examined. There were no differences as to the incidence of childhood sexual or physical abuse between patients with vulvodynia and either those with general dermatology complaints or those with chronic vulvar symptoms due to objective disease. CONCLUSION: There is no evidence from these data that women with vulvodynia experience a higher incidence of sexual or physical abuse during childhood as compared to women in a general dermatology office or women with chronic vulvar symptoms from specific, observable pathology.
Adult↗